A Novel Anti-Endotoxin Peptide for Septic Shock Project Summary The purpose of this Phase I SBIR proposal is to evaluate the feasibility of a novel peptide, CN16, for the treatment of septic shock. Current therapeutic interventions for endotoxin shock and septic shock fail to demonstrate effective treatment for patients with sepsis. Recently, we identified the peptide, CN16, for its potent anti-endotoxin activity. Because CN16 is so effective in blocking the function of gram-negative bacterial lipopolysaccharides (LSP) and its potential beneficial effects in animal models of septic shock, we hypothesize that CN16 will be an effective drug candidate for treating septic shock in patients. The market for a drug candidate for septic shock is $17 Billion* ($22,100/per patient) in the US alone. Approximately 1.5 M people world-wide suffer from sepsis annually;700,000 new cases of sepsis annually are diagnosed in the U.S. with a 30-50% mortality rate*. The incidence of sepsis is expected to increase over the next decade due to increasing number of elderly patients and increased uses of immune suppressive therapies. Our focus for this Phase-I study is to validate CN16 as therapeutic candidate for the prevention of septic shock mediated by LPS in vitro and in vivo using two sepsis models in mice. These studies will lead to improved understanding of the role of CN16 in the biology to gram-negative bacterial sepsis/septic shock. In addition the results of these studies will form the basis for a SBIR phase-II study, which will focus on pre-clinical development of the drug candidate. Our long-range goal is to develop an anti-endotoxin therapeutic agent for gram-negative bacterial sepsis. The potential therapeutic applications may include treatment for patients with peritonitis, sepsis, and/or septic shock. *Angus D, et al. Crit Care Med 2001;29(7): 1303-1310. PUBLIC HEALTH RELEVANCE: A Novel Anti-Endotoxin Peptide for Septic Shock Project Narrative We are proposing a feasibility study for a therapeutic drug candidate, the anti-endotoxin peptide CN16, for the treatment of sepsis. CN16 has been shown to prevent the interaction of an important sepsis mediator with its target and thus prevent the initiation of a self-amplifying cascade of inflammatory events with a possibly fatal outcome. The data obtained in this study may support further development of CN16 as a clinical development candidate.